X-ray Fluorescence Microscopy: A Tool for Biology, Life Science & Nanomedicine

Trace elements, in particular metals, play a significant role in most known life forms. It is estimated that one-third of all known proteins contain metal cofactors, and the majority of these function as essential metalloenzymes catalyzing biochemical reactions. Trace metals are increasingly recognized as having a critical impact on human health both in their natural occurrence and via therapeutic drugs (e.g., environmental exposure to heavy metals, treatment with cisplatin-based drugs in chemotherapy, ...), and in diseases such as Alzheimer’s. Quantitative study of the distribution of trace elements on the cellular and subcellular level provide important information about functions and pathways of metalloproteins and therapeutic approaches, especially in conjunction with the local chemical state of the elements of interest. In the area of nanomedicine, the development of nanocomposites, often metal-based, that combine properties for in vivo imaging, therapy, and specific targeting, is an area that promises significant opportunities. Hard X-ray fluorescence microscopy is a powerful technique to map and quantify element distributions in biological specimens such as cells and bacteria. It provides attogram sensitivity for transition metals like Cu, Zn, and other biologically relevant trace elements, at suboptical spatial resolution (currently ~150 nm), combined with the capability to penetrate whole cells and thick tissue sections. The possibility of selecting the incident x-ray energy with a bandwidth of dE/E= 10-4 enables microspectroscopy and chemical state mapping to determine the speciation of elements of interest. These unique capabilities of x-ray fluorescence microscopy have been employed in diverse biomedical applications, and complement other modern microscopy techniques. We will discuss the instrumentation and methods we have implemented, including data analysis, differential phase contrast to visualize soft tissue and fast fly-scanning. We will demonstrate their application in several current studies, such as nanocomposites for targeting specific locations in biological cells for eventual in vivo use